Triptolide has piqued the interest of the organic and medicinal chemistry communities in recent decades due to its fascinating structural characteristics and prospective diverse pharmacological actions. However, its low water solubility and oral bioavailability, uncertain mode of action and severe toxicity, natural scarcity and complexity in synthesis have severely hampered its therapeutic usefulness. As a result, several clever total synthesis algorithms have been created to avoid such difficulties. Various triptolide derivatives have been produced and evaluated in the hunt for new drug-like derivatives for possible anticancer, anti-inflammatory, immunosuppressive and anti-agents, Alzheimer's among other things. Meanwhile, by developing and synthesising diverse bioactive probes, certain molecular targets responsible for numerous pharmacological actions have been identified.